Radiation Treatment Planning and Delivery for Moving Targets in the Heart

ABSTRACT

Method and systems are disclosed for radiating a moving target inside a heart. The method includes acquiring sequential volumetric representations of an area of the heart and defining a target tissue region and/or a radiation sensitive structure region in 3D for a first of the representations. The target tissue region and/or radiation sensitive structure region are identified for another of the representations by an analysis of the area of the heart from the first representation and the other representation. Radiation beams to the target tissue region are fired in response to the identified target tissue region and/or radiation sensitive structure region from the other representation.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a Continuation of U.S. Ser. No. 13/619,064 filedSep. 14, 2012; which is a Continuation of U.S. Ser. No. 12/900,717 filedOct. 8, 2010 (now U.S. Pat. No. 8,345,821), which application is aContinuation of U.S. Ser. No. 12/077,016 filed Mar. 14, 2008, whichapplication claims the benefit under 35 USC 119(e) of U.S. ProvisionalApplication No. 60/918,540 filed Mar. 16, 2007. The full disclosures,each of which are incorporated herein by reference in their entirety forall purposes.

This application is related to U.S. patent Ser. No. 11/971,399 filedJan. 9, 2008, entitled “Depositing Radiation In Heart Muscle UnderUltrasound Guidance;” U.S. patent Ser. No. 11/971,725 filed on Jan. 9,2008, entitled “Method for Depositing Radiation in Heart Muscle;” andU.S. Provisional Application No. 60/975,373 filed on Sep. 26, 2007,entitled “Radiosurgical Ablation of the Myocardium;” the fulldisclosures of which are incorporated herein by reference in theirentirety.

BACKGROUND OF THE INVENTION

The present invention generally provides improved methods, devices, andsystems for treatment of tissue, in many cases by directing radiationfrom outside the body toward an internal target tissue. Exemplaryembodiments may deposit a specified radiation dose at a target in theheart muscle while limiting or minimizing the dose received by adjoiningradiation sensitive structures.

In the past, targets such as tumors in the head, spine, abdomen andlungs have been successfully treated by using radiosurgery. Duringradiosurgery, the target is bombarded with a series of beams of ionizingradiation (for example, a series of MeV X-ray beams) fired from variousdifferent positions and orientations by a radiation delivery system. Thebeams can be directed through intermediate tissue toward the targettissue so as to affect the tumor biology. The beam trajectories helplimit the radiation exposure to the intermediate and other collateraltissues, using the cumulative radiation dose at the target to treat thetumor. The CyberKnife™ Radiosurgical System (Accuray Inc.) and theTrilogy™ radiosurgical system (Varian Medical Systems) are two suchradiation delivery systems.

Modern robotic radiosurgical systems may incorporate imaging into thetreatment system so as to verify the position of the target tissuewithout having to rely on rigid frameworks affixing the patient to apatient support. Some systems also have an ability to treat tissues thatmove during respiration, and this has significantly broadened the numberof patients that can benefit from radiosurgery. It has also previouslybeen proposed to make use of radiosurgical treatments for treatment ofother tissues that undergo physiological movements, including thedirecting of radiation toward selected areas of the heart for treatmentof atrial fibrillation.

During atrial fibrillation, the atria lose their organized pumpingaction. In normal sinus rhythm, the atria contract, the valves open, andblood fills the ventricles (the lower chambers). The ventricles thencontract to complete the organized cycle of each heart beat. Atrialfibrillation has been characterized as a storm of electrical energy thattravels across the atria, causing these upper chambers of the heart toquiver or fibrillate. During atrial fibrillation, the blood is not ableto empty efficiently from the atria into the ventricles with each heartbeat. By directing ionizing radiation toward the heart based on lesionpatterns used in open surgical atrial fibrillation therapies (such asthe Maze procedure), the resulting scar tissue may prevent recirculatingelectrical signals and thereby diminish or eliminate the atrialfibrillation.

While the proposed radiosurgical treatments of atrial fibrillation offerbenefits by significantly reducing trauma for heart patients,improvements to existing radiosurgical systems may be helpful to expandthe use of such therapies. For example, movement of the tissues of theheart during a heartbeat may be significantly more rapid than movementsof lung tumors induced by respiration. While well suited for treatmentof lung tissues and the like, existing systems used to verify targetregistration may also limit radiation exposure of collateral tissuesand/or avoid delays in the procedure by limiting the rate at which x-rayimages are acquired during treatment. As several radiation-sensitivestructures are in and/or near the heart, and as the treatment time for asingle heart patient may be as long as 30 minutes or more, increasingthe imaging rate and/or delaying the radiation beams when the targettissue is not sufficiently aligned may be undesirable in many cases.

In light of the above, it would be desirable to provide improveddevices, systems, and methods for treating moving tissues of a patient,particularly by directing radiation from outside the patient and intotarget tissues of a heart. It would be particularly beneficial if theseimprovements were compatible with (and could be implemented bymodification of) existing radiosurgical systems, ideally withoutsignificantly increasing the exposure of patients to incidental imagingradiation, without increasing the costs so much as to make thesetreatments unavailable to many patients, and/or without unnecessarilydegrading the accuracy of the treatments and without causing collateraldamage to the healthy tissue despite the movement of the target tissuesduring beating of the heart.

BRIEF SUMMARY OF THE INVENTION

The present invention generally provides improved medical devices,systems, and methods, particularly for radiation treatment planning anddelivery for moving tissues in a heart. The invention allows improvedradiosurgical treatment of tissues of the heart, often enhancing thecapabilities of existing robotic radiosurgical systems for targetingtissues of the heart to mitigate arrhythmias such as atrial fibrillationor the like.

In one embodiment, a method is disclosed for radiating a moving targetinside a heart comprising acquiring sequential volumetricrepresentations of an area of the heart and defining a target tissueregion and/or a radiation sensitive structure region in 3-dimensions(3D) for a first of the representations. The target tissue region and/orradiation sensitive structure region are identified for another of therepresentations by an analysis of the area of the heart from the firstrepresentation and the other representation. Radiation beams to thetarget tissue region are fired in response to the identified targettissue region and/or radiation sensitive structure region from the otherrepresentation.

In another embodiment, a method is disclosed for radiating a movingtarget of a wall of a heart comprising acquiring at least one volume ofthe heart and defining the target tissue region and/or criticalstructure region in 3D so that the target tissue region extends throughthe wall of the heart. A dose distribution is computed and radiationbeams are fired to the target to obtain the simulated dose distributiontransmurally through the wall of the heart.

In another embodiment, a method is disclosed for radiating a movingtarget inside a heart comprising acquiring a computed tomography (CT)volume and defining a transmural target tissue region. A dosedistribution is computed and visualized using volume or surfacerendering in 3D so as to verify transmurality.

In another embodiment, a system is disclosed for radiating a movingtarget inside a heart comprising a volume acquisition system foracquiring at least one CT volume of an area of the heart and a processorcoupled to the image acquisition system. The processor is configured fordefining the target tissue region and/or critical structure region in 3Dand computing a dose distribution. A robot is coupled to the processorand a radiation beam source is supported by the robot and is coupled tothe processor. The processor controls the firing of a series of theradiation beams from the radiation source so as to treat the targettissue region.

In another embodiment, a system is disclosed for radiating a movingtarget inside a heart comprising a volume acquisition system foracquiring a computed tomography (CT) volume and a processor coupled tothe image acquisition system. the processor is configured for defining atransmural target tissue region and computing a dose distribution. Avisualization system is used for visualizing the dose distribution usingvolume or surface rendering in 3-dimensions (3D) so as to verifytransmurality.

Many different types of modeling may be used with the method andsystems, including (1) volume rendering, (2) maximum intensityprojection, (3) minimum intensity projection, (4) X-ray projection, (5)haptic feedback, (6). virtual fly-through, (7) stereoscopic 3Drendering, (8) virtual reality and (9) multi-planar, oblique and curvedreconstruction. In some embodiments the contours of the target tissueregion and/or a radiation sensitive structure region are outlined in 3D.In some embodiments an electrogram may be registered to the CT volumes.In some embodiments the moving target is a wall of a heart and themethods and systems ensure transmurality of the target.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exemplary CyberKnife stereotactic radiosurgery system foruse in embodiments of the invention.

FIG. 2 schematically illustrates locations of the target, the radiationsensitive structures, the nodes and the beams in the CyberKnife system.

FIG. 3 graphically illustrates an EKG waveform showing the phases whereCT volumes may be acquired.

FIG. 4 illustrates a screenshot of a display showing an output obtainedusing an exemplary software application for loading and proscribing atarget in moving tissue.

FIGS. 5(a), 5(b) and 5(c) illustrate one example of a target shape to bedefined in the case of PV ostia to ensure transmurality.

FIG. 6 schematically illustrates a method for treating a target tissueusing a radiosurgical system.

DETAILED DESCRIPTION OF THE INVENTION

The present invention generally provides improved devices, systems, andmethods for treatment of tissue, often using radiosurgical systems. Theinvention is particularly well suited for tracking of moving tissuessuch as tissues of the heart and tissue structures adjacent the heartthat move with the cardiac or heartbeat cycles. Alternatively, it isalso suited for tracking of moving tissues in the heart and its adjacentstructures due to respiration. The invention may take advantage ofstructures and methods which have been developed for treating tumors,particularly those which are associated with treatments of tissuestructures that move with the respiration cycle. A variety of differingembodiments may be employed, with the following description presentingexemplary embodiments that do not necessarily limit the scope of theinvention.

Radiosurgery is a known method of treating targets in the body, such astumors in the head, spine, abdomen and lungs. During radiosurgery, thetarget is bombarded with a series of MeV X-ray beams fired from variousdifferent positions and orientations by using a radiation deliverysystem, to affect the tumor biology using the cumulative radiation doseat the target. The radiation can be delivered invasively in conjunctionwith traditional scalpel surgery, or through a percutaneous catheter.Radiation can also be delivered non-invasively from outside the body,through overlying tissue. CyberKnife™ (Accuray Inc.) and Trilogy™(Varian Medical Systems) are two such radiation delivery systems.Advances in stereotactic surgery have provided increased accuracy inregistering the position of tissue targeted for treatment and aradiation source. For example, see U.S. Pat. Nos. 6,351,662 and6,402,762. Stereotactic radiosurgery systems may be commerciallyavailable from ACCURAY, INC. of Sunnyvale, Calif., and BRAINLAB. TheAccuray Cyberknife™ stereotactic radiosurgery system has reportedly beenused to provide targeted, painless, and fast treatment of tumors.

Improvements in imaging and computer technology have led to advances inradiation treatment, often for targeting tumors of the spine and brain.The introduction of CT scanners enables surgeons and radiationoncologist to better define the location and shape of a tumor. Furtherimprovements in imaging technology include MRI, ultrasound, fluoroscopyand PET scanners. In addition, radiation therapy has also been aided byenhancements in ancillary technologies such as simulators to helpposition patients and advanced computers to improve treatment planningto enable the radiation oncologist to deliver radiation from a number ofdifferent angles. Computer technology has been introduced that enableradiation oncologists to link CT scanners to radiation therapy, makingtreatment more precise and treatment planning faster and more accurate,thereby making more complex plans available. Such advancements allowintegrated conformal therapy, in which the radiation beam conforms to anactual shape of a tumor to minimize collateral damage to the surroundinghealthy tissue. By combining simulators and imaging and treatmentplanning computers, the irradiation can be precisely administered.

The present invention may take advantage of many components included inor derived from known radiation delivery system components. Suitablesystem components may comprise:

-   -   1. A linear accelerator (Linac) capable of generating the X-ray        beam.    -   2. A mechanism to position and orient the X-ray beam.    -   3. A patient registration system to position and orient the        target in the coordinate system of the delivery system.    -   4. A tracking system for tracking the target during treatment in        case the target changes shape or moves between the time of, for        example, a CT exam and the time of treatment, and/or during        treatment.    -   5. A couch capable of positioning the target (patient)        independent of the mechanism described in #2 above.

In exemplary CyberKnife-based systems, the above 5 items may correspondto:

-   -   1. A 6 MeV X-band X-ray Linac    -   2. A 6 degree-of-freedom (DOF) robotic manipulator.    -   3. A patient registration system consisting of:        -   Two ceiling-mounted diagnostic X-ray sources        -   Two amorphous silicon image detectors mounted on the floor.    -   4. During treatment, two orthogonal X-rays are taken and        registered with the CT data by cross-correlating the X-rays with        simulated X-rays generated by CT data, called digitally        reconstructed radiographs (DRR).    -   5. The tracking system may include several light-emitting diodes        (LEDs) mounted on the patent's skin to provide additional        information at a rate faster than what X-rays alone may provide.    -   6. A couch with 5 DOF.

An exemplary Cyberknife stereotactic radiosurgery system 10 isillustrated in FIG. 1. Radiosurgery system 10 has a single source ofradiation, which moves about relative to a patient. Radiosurgery system10 includes a lightweight linear accelerator 12 mounted to a highlymaneuverable robotic arm 14. An image guidance system 16 uses imageregistration techniques to determine the treatment site coordinates withrespect to linear accelerator 12, and transmits the target coordinatesto robot arm 14 which then directs a radiation beam to the treatmentsite. When the target moves, system 10 detects the change and correctsthe beam pointing in real-time or near real-time. Real-time or nearreal-time image guidance may avoid any need for skeletal fixation torigidly immobilize the target.

System 10 makes use of robot arm 14 and linear accelerator 12 undercomputer control. Image guidance system 16 includes diagnostic x-raysource 18 and image detectors 20, this imaging hardware comprising twofixed diagnostics fluoroscopes. These fluoroscopes provide a stationaryframe of reference for locating the patient's anatomy, which, in turn,has a known relationship to the reference frame of robot arm 14 andlinear accelerator 12. Image guidance system 16 can monitor patientmovement and automatically adjust system 10 to maintain the radiationbeam directed at the selected target tissue. Rather than make use ofradiosurgery system 10 and related externally applied radiosurgicaltechniques to tumors of the spine and brain tissues, the inventionapplies system 10 to numerous cardiac conditions, and in one exemplarymethod to the treatment of atrial fibrillation (AF).

Tradition radiosurgery instruments without image guidance technologyrely on stereotactic metal frames screwed into the patient's skull toaccurately target a tumor. Traditional radiosurgery has its drawbacks,the biggest of which relate to the use of the frame, including the painand difficulty of accurately reattaching the frame in precisely the samelocation, along with the inability to target tissues other than those inthe neck and head. Conventional linear accelerators for these systemscan also be the size and weight of an automobile. Frame-basedradiosurgery is generally limited to isocentric or spherical targettreatments. To allow a device which can precisely pinpoint and treattissues throughout the body, system 10 makes use of a portable linearaccelerator, such as those originally designed for industrialinspections, which can be carried on a person's back. Linearaccelerators may be commercially available from SCHONBERG RESEARCHGROUP, SIEMENS, PICKER INTERNATIONAL INC. or VARIAN.

System 10 allows intensity modulated radiation therapy. Usingcomputerized planning and delivery, intensity modulated radiationtherapy conforms the radiation to the shape of (for example) a tumor. Byusing computers to analyze the treatment planning options, multiplebeams of radiation match the shape of the tumor. To allow radiosurgery,system 10 can apply intense doses of high-energy radiation to destroytissue in a single treatment. Radiosurgery with system 10 uses precisespatial localization and large numbers of cross-fired radiation beams.Because of the high dosage of radiation being administered, suchradiosurgery is generally more precise than other radiation treatments,with targeting accuracies of 1 to 2 mm.

Linear accelerator 12 is robotically controlled and delivers pin-pointradiation to target regions throughout the body of the patient.Radiation may be administered by using a portable linear acceleratorsuch as that illustrated in FIG. 1. Larger linear accelerators may alsogenerate the radiation in some embodiments. Such linear accelerators maybe mounted on a large rotating arm that travels around the patient,delivering radiation in constant arcs. This process delivers radiationto the target tissue and also irradiates a certain amount of surroundingtissue. As a result, such radiation therapy may be administered in aseries of relatively small doses given daily over a period of severalweeks, a process referred to as fractionation. Each radiation dose cancreate some collateral damage to the healthy surrounding tissue.

In the exemplary embodiment, robot arm 14 of system 10 is part of a purerobotics system, providing six degree of freedom range of motion. Inuse, the surgeon basically pushes a button and the non-invasiveprocedure is performed automatically with the image guidance systemcontinuously checking and re-checking the position of the target tissueand the precision with which linear accelerator 12 is firing radiationat the tumor. Image guidance system provides ultrasound guidance thatgives the surgeon the position of internal organs. Image guidance systemcontinuously checks, during a procedure, that the radiation beam isdirected to the target. Alternatively the image guidance system includesan X-ray imaging system as is the case with the traditional AccurayCyberKnife™ radiosurgery system. The exemplary image guidance systemtakes the surgeon's hand out of the loop. The surgeon may not even be inthe operating room with the patient. Instead, the image guidance systemguides the procedure automatically on a real-time basis. By combiningadvanced image guidance and robotics, system 10 has proven effective intreating head and neck tumors without having to resort to stereotacticmetal frame screwed into the skull of a patient.

The target shape may be a three-dimensional shape and may include (1)volume rendering, (2) maximum intensity projection, (3) minimumintensity projection, (4) X-ray projection, (5) haptic feedback, (6).virtual fly-through, (7) stereoscopic 3D rendering, (8) virtual reality,and (9) multi-planar, oblique and curved reconstruction.

The system 10 creates the target shape to encompass (including orsurrounding) the anatomical site. The anatomical site may include anostium of a pulmonary vein (PV), a cavotricuspid isthmus (CTI), anAtrioventricular (AV) node or junction, Sinoatrial (SA) node,His-Purkinje fibers, or ablation of areas necessary to control and treataberrant arrhythmias, an atrial or ventricular site, neural fibers nearor adjacent to the heart (ganglionic) or neural fibers in the chest orneck.

Once the target position is determined, the coordinates are relayed torobot arm 14, which adjusts the pointing of linear accelerator 12 andradiation is delivered. The speed of the imaging process allows thesystem to detect and adjust to changes in target position in less thanone second. The linear accelerator is then moved to a new position andthe process is repeated. Alternative systems may make use of lasertriangulation, which refers to a method of using so-called laser tattoosto mark external points on the skin's surface so as to target thelocation of internal organs and critical structures. An alternativesystem commercialized by BRAINLAB uses a slightly different approachthat measures chest wall movements.

The system is capable of directing one or more doses of radiation fromoutside of the patient's body toward the target shape to ablate thetarget shape. The quantity of absorbed in a tissue is the “dose” withthe SI unit Gray (Gy=J/kg). The dose is strongly dependent on the typeof radiation and the time span, also called “dwell time”. An applicationdose rate is the dose of radiation per time (delivered or received). Thedose rate delivered by a source depends on the activity of the sourceand the radionuclide that it contains. Biological effects of theabsorbed radiation are dependent on the type of radiation and the typeof tissue which is irradiated. Both total radiation dose and dose rateare important, since damage caused by radiation can be repaired betweenfractionated doses or during low dose rate exposure. The target doserate may be between 15 to 80 Gy, preferably, between 25 to 40 Gy toachieve histological change at the target site without harm to othertissue. In one embodiment, the accuracy of is better than 2 mm, which iswithin the range of cardiac motion certain portions of the heart at orwithin 2 mm plus or minus.

System 10 combines robotics and advanced image-guidance to deliver trueframeless radiosurgery. Multiple beams of image guided radiation aredelivered by robot arm 14 mounted linear accelerator 12. The radiationcan converge upon a tumor, destroying it while minimizing exposure tosurrounding healthy tissue. Elimination of a stereotactic frame throughthe use of image guided robotics enables system 10 to treat targetslocated throughout the body, not just in the head. Radiosurgery is thuspossible in areas such as the spine that have traditionally beendifficult to treat in the past with radiosurgery, and for pediatricpatients such as infants, whose skulls are too thin and fragile toundergo frame-based treatment.

System 10 allows ablation of tissue anywhere in the patient's body. Thepresent invention uses high energy x-ray irradiation from a linearaccelerator mounted on a robot arm to produce ablation of target tissue.In one example, system 10 is used to ablate tumors or other defects ofthe heart treatable with radiation.

Advantages of system 10 include a treatment which can be provided on anoutpatient basis, providing a painless option without the risk ofcomplications associated with open surgery. Treatment may be applied ina single-fraction or hypo-fractionated radiosurgery (usually 2 to 5fractions) for treatment near sensitive structures. System 10 providesflexibility in approach through computer control of flexible robotic arm14 for access to hard-to-reach locations. System 10 is capable ofirradiating with millimeter accuracy. System 10 also has the ability tocomprehensively treat multiple target shapes. System 10 allowsisocentric (for spherical) or non-isocentric (for irregularly shaped)target shapes. The creation of the target shapes also takes into accountcritical surrounding structures, and through the use of robotic arm 14,harm to the critical structures surrounding may be reduced.Sophisticated software allows for complex radiation dose planning inwhich critical structures are identified and protected from harmfullevels of radiation dose. After careful planning, the precise roboticarm can stretch to hard-to-reach areas. The precise radiation deliveredfrom the arm then minimizes the chance of injury to critical surroundingstructures, with near-real-time image-guidance system eliminating theneed for rigid immobilization, allowing robot arm 12 to track the bodythroughout the treatment.

It may be advantageous to, for a moving target inside the heart:

-   -   1. Proscribe a dose distribution to a target region in moving        tissue,    -   2. Simulate the dose distribution, and    -   3. Deliver the specified dose.

During treatment planning for system 10, beam nodes 30 and weights maybe selected by a computer programming module to:

-   -   1. Deliver the proscribed dose to a target 32.    -   2. Avoid or minimize the dose delivered to radiation sensitive        structures 34, such as shown in FIG. 2.

Before a treatment session, a CT volume of the target vicinity isacquired. Other imaging modalities such as MRI, PET and ultrasound mayalso be used. The user defines the target and any radiation sensitivestructures by outlining a series of contours in slices through the CTvolume. A computer program then generates the set of nodes 30 from whicha set of beams 36 will be fired and the weights for each of the beams.Alternatively, the user selects the nodes and the computer programgenerates the weights.

If the target is inside the heart, a series of CT volumes, called avolumetric movie may be acquired to capture the motion of the target.The definition of the target and the radiation sensitive structures canbe time consuming since the user may outline contours in each of thevolumes in the volumetric movie. The volumetric movie may be acquired asa function of a physiologic waveform such as EKG, respiratory signal orboth.

In the case where the target is inside the heart on heart muscle,radiosurgical ablation creates scar tissue and eliminates abnormallyconducting tissue. Radiosurgical ablation thus has the ability tosuppress arrhythmias by creating lesions at targets such as thecavotricuspid isthmus and pulmonary vein ostia. One of key objectiveswhen defining the target on heart muscle is to ensure that the target istransmural, i.e., covers the entire thickness of the heart muscle.

The methods for defining targets in the body using CT involves the userdrawing 2-dimensional contours in axial, sagittal, coronal or obliqueslices generated from the CT volume. Since heart is a complex3-dimensional shape, it is not easy to draw such contours on heartmuscle in above mentioned slices to ensure that target transmurality isachieved. Embodiments of the invention eliminates this limitation byallowing target definition in 3-dimensions, and providing techniques tovisualize the target on heart muscle to ensure that the target is infact transmural.

Detailed Description of an Exemplary Method for Implementation in aHeart Treatment System

In an exemplary new method, the user defines the target and theradiation sensitive structures much more quickly. The steps of thisembodiment method may include the following:

-   -   1. Acquire a series of M CT volumes, CT(j), j=0, . . . , M−1, of        the heart over one cardiac cycle with the patient holding        his/her breath. Use a high speed CT scanner such as 64-slice        Siemens SOMOTOM Definition to acquire CT volumes quickly, e.g.        one volume in 83 ms. Contrast agents may be used. FIG. 3 shows a        typical EKG waveform with M=10 phases where 10 CT volumes are        acquired. Alternatively, the CT volumes, CT(j) could be acquired        over a respiratory cycle. Additionally, the CT volumes, CT(j)        may be acquired over a respiratory cycle, yet triggered to an        EKG cycle.    -   2. Load all the M CT data volumes (here in forth known as        “volumetric movie”) in to a data visualization computer software        application module running on the processor of system 10 coupled        to a suitable display device, or on a processor capable of        communicating to the processor of system 10. FIG. 4 shows a        screenshot of a display of an exemplary such application.        Top-left, bottom-left, bottom-right views, called multi-planar        reconstruction-views (or MPR views), are axial, sagittal and        coronal slices through a single volume in the volumetric movie,        respectively. Top right is a view, called volume rendered view        (or VR view), containing a 3D representation of the volume,        generated using a technique called volume rendering. The VR view        also covers techniques of generating other 3D representations        such as (a) maximum intensity projection, (b) minimum intensity        projection and (c) X-ray projection.    -   3. Define the target region and radiation sensitive structures        in 3D using, for example, the VR-view. The user optionally drags        and drops a geometric-shape, such as a doughnut, at the target        region, such as the ostia of a pulmonary vein. The application        provides 3D tools to orient and place the doughnut in the        correct place and orientation. The application may also provide        alternative MPR-views, such as a view orthogonal to the viewing        direction, oblique reconstructed views, and curved reconstructed        views.    -   4. Additionally, surface detection techniques such as “marching        cubes” can be used to detect the 3-dimensional surfaces        corresponding to the borders of myocardial tissue. Using the        tools provided, the user can edit these surfaces to define the        target. Editing includes cutting a surfaces, clipping using a        bounding box.    -   FIGS. 5(a), 5(b) and 5(c) show the target shape to be defined in        the case of PV ostia to ensure transmurality. FIG. 5(a) shows        the anatomy including the left atrium 40 and pulmonary vein 42.        FIG. 5(c) shows the target shape 44, a hollow cylinder-like        shape. This ensures that the area ablated covers the full        thickness of the walls of the PV ostium. The user can define        this shape in 3-dimensions using the techniques described above.        If they were to define this target in 2-dimensional slices, it        would be very difficult.    -   Alternatively, the user can define a target such as the        cylinder-shape 46 shown in FIG. 5(b), which encompasses the PV        ostium and the blood inside it as well. This shape, called        Planning Target Volume for Optimization (PTVO) can be used by        the treatment planning software to generate the node-set. To        quantify the dose delivered to the tissue, Planning Target        Volume for Evaluation (PTVE), as shown in FIG. 5(c) can be used.        In this case both PTVO and PTVE must be defined by the user to        ensure transmurality. PTVO can also be automatically generated        from PTVE.    -   If an electrogram is available, it can be registered to the CT        data set and shown to the user. The user then sees the areas        where the electrical activity is abnormal in the electrogram and        can define the target in the electrogram it self in        3-dimensions. Since the CT is registered to the electrogram,        this target can then be used to define PTVE or PTVO.        Alternatively, the user can define the target in CT and        visualize it in the electrogram in 3-dimensions to ensure that        the target in fact covers areas where the electrical activity is        high.    -   5. Other types of target shapes, such as spheres and polyhedrons        can be used. Other types of target regions, such as,        cavotricuspid isthmus or AV node can be used. Alternatively, the        target and critical structure shapes can be defined using a 3D        mouse or a 3D bumper tool, an improvement over the 2D mouse and        2D bumper tool found in MultiPlan™ Treatment Planning        Workstation (Accuray Incorporated).    -   6. Optionally, the application provides the ability to view the        target area from inside the heart chambers and vessels using a        technique called “virtual-fly though”. An airplane rudder        control-like interface provides the ability for the user to        visualize the myocardial walls from within the heart. The user        gets the sensation that he/she is flying inside the heart        chambers. Using various controls, they can bank, accelerate,        decelerate, pull-up, nose-down inside the heart chambers. The        user can also place the doughnut-shaped target, or any        other-shaped target, at pulmonary vein ostia or any other area        inside the heart.    -   7. Optionally, the application also provides force feedback to        the user. Instead or in addition to a computer mouse, the user        can use a haptic feedback device such as Omega Haptic Device        (Force Dimension, Inc.). When the user grabs the target and        moves it towards the target region, if the geometric shape is        inside the blood, he/she will feel very little resistance to        movement. If the geometric shape impinges the heart wall, he/she        will feel some resistance, possibly the sensation of pushing        against soft-tissue, or a rubber-like material.    -   8. Optionally, the application may provide a stereoscopic 3D        rendering to the user. In stereoscopic 3D rendering the VR-view        is generated twice using two different vantage points, typically        separated by the average distance between human eyes. These left        and right images are then shown to the left and right eyes of        the user separately simultaneously or in rapid sequence. There        are a number of display devices to view stereoscopic 3D        renderings:        -   a. Stereo goggles using polarizing lenses or switching            displays.        -   b. Stereoscopic monitors    -   9. The system loads the other CT volumes from the volumetric        movie. It then automatically finds the location of the soft        tissue region covered by the aforementioned geometric shape in        all the volumes. Following this, it finds the motion of the soft        tissue region throughout the cardiac cycle by using all the        volumes. Correlation of a similarity function, based on CT        intensities, higher order derivatives thereof, or features can        be used to find the motion. One exemplary method and/or system        (here employing mutual information as a similarity measure) that        may be suitable for use in embodiments of the invention (without        limiting other embodiments that may use other approaches) is        described in an article by L. Zollei, E. Crimson, A. Norbash, W.        Wells, entitled “2D-3D rigid registration of x-ray fluoroscopy        and CT images using mutual information and sparsely sampled        histogram estimators,” CVPR 2001, which is incorporated herein        by reference. Another exemplary method and/or system can be        found in the deformable registration method described by J-P        Thirion entitled “Image Matching as a diffusion process: an        analogy with Maxwell's Demons”, Medical Image Analysis (1998)        Volume 2, Number 3, pp 243-260, Oxford University Press.    -   10A. The system then computes the dose distributions for each of        the volumes in the volumetric movie. From this, it computes the        average dose distribution.    -   10B. Alternatively, the motion of the target or critical        structures that cannot be tracked can be accounted for by        expanding the target and critical volumes with a margin that is        based on motion estimates. The margin can be large enough to        include the full amplitude of motion or it could be large enough        to include the target a large percentage of the time. Expanding        the target region by the full extent of the motion will result        in more tissue destruction than is necessary. In radiosurgical        treatment of tumors, margins have the benefit of destroying any        microscopic extension of the cancer that is not visible in the        images. However, in radiosurgical treatment of arrhythmias, the        target structure is well known and does not include any        extension, therefore, the margin should be minimized. Margins        can be calculated to include the target a large percentage of        the time by determining the three dimensional probability        density function for the target position and then setting the        margin to include some fraction of the integrated probability.        The dose calculation can then be modified based on the fraction        of the treatment when the target is within the volume. Multiple        margins calculated with different probability levels can be used        in the dose calculation. For example, if a margin is drawn        around a target region to include the complete target 80% of the        time, the minimum dose can be estimated as 0.8*min80, where        min80 represents the minimum dose within the margin that        includes the entire target 80% of the time.    -   In this estimate, target is considered to receive no dose during        the time it spends outside of the margin. If an additional        margin is drawn to include the target region 95% of the time,        the minimum dose can be estimated as the lesser of (min80) and        (0.8*min80+0.15*min95), where min80 is defined as above and        min90 represents the minimum dose within the margin that        includes the entire target 95% of the time. These calculations        will underestimate the minimum dose to the target less than        using a margin that includes the target 100% of the time.    -   Similar calculations can be made for the maximum dose to        critical structures. For example, if a margin is drawn to        include the complete critical structure 80% of the time, the        maximum dose to any point in the critical structure can be        calculated as (0.8*max80+0.2*maxField), where max80 is the        maximum dose within the margin that includes the target 80% of        the time and maxField represents the maximum dose in the field.        If an additional margin is drawn to include the critical        structure 100% of the time, the maximum dose to any point in the        critical structure can be calculated as the greater of max80 and        (0.8*max80+0.2*max100), where max80 is defined as above and        max100 is the maximum dose within the margin that includes the        critical structure 100% of the time. This will overestimate the        maximum dose to the critical structure less than a margin based        on including the critical structure 100% of the time.    -   Isotropic or anisotropic margins can be used to account for the        motion. Anisotropic margins can be calculated by moving each        surface point in an outward surface normal direction by a        distance equal to the radius of a margin ellipsoid in the same        direction as the outward surface normal. Accuracy may be        improved by defining the margin ellipsoid such that its        principle axes are aligned with the principle axis of the motion        of the target or critical structure.    -   Margin estimates do not require full volumetric motion        information from the target. An estimate of the target motion        can be determined by the position measurements for one point on        the target at multiple times during the cardiac cycle. This can        be obtained from simultaneous biplanar fluoroscopic images        showing the tip of a catheter that has been placed in the heart        touching the cardiac structure of interest. Alternatively,        real-time 3D ultrasound could be used to determine the motion of        structures of interest non-invasively.    -   11. The robot then fires the beams from predetermined locations        to create the simulated dose distribution.    -   12. Alternatively, the user may visualize the 3D or 4D dose        distributions using a volume rendering of the dose distribution.        Optionally, 3D fly though and haptic feedback can be used to        visualize and interact with the 3D or 4D dose distributions.

Referring now to FIG. 6, a relatively simple treatment flowchart 50 canrepresent imaging 52, planning 54, and treatment 56 steps and/orstructures used before and during radiosurgical treatment according toembodiments of the present invention. Imaging 52, planning 54, andtreatment 56 structures may include an associated processor module. Theprocessor modules will typically comprise computer processing hardwareand/or software, with the software typically being in the form oftangible media embodying computer-readable instructions or code forimplementing one, some, or all of the method steps described herein.Suitable tangible media may comprise a random access memory (RAM), aread-only memory (ROM), a volatile memory, a non-volatile memory, aflash memory, a magnetic recording media (such as a hard disk, a floppydisk, or the like), an optical recording media (such as a compact disk(CD), a digital video disk (DVD), a read-only compact disk, a read/writecompact disk, a memory stick, or the like). The various modulesdescribed herein may be implemented in a single processor board of asingle general purpose computer, or may be run on several differentprocessor boards of multiple proprietary computers, with the code, data,and signals being transmitted between the processor boards using a bus,a network (such as an Ethernet, intranet, or internet), via tangiblerecording media, using wireless telemetry, or the like. The code may bewritten as a monolithic software program, but will typically comprise avariety of separate subroutines and/or programs handling differingfunctions in any of a wide variety of software architectures, dataprocessing arrangements, and the like. Nonetheless, breaking thefunctionality of the program into separate modules is useful forunderstanding the capabilities of the various aspects of the invention.

Addressing the imaging block 52 of block diagram 50 in FIG. 6, atime-sequence of 3-D volumes may be acquired using computed tomography(CT), magnetic resonance imaging (MRI), ultrasound imaging, X-rayimaging, optical coherence tomography, a combination of these or otherimaging modalities, and/or the like. In some embodiments, correspondingEKG signals may also be received by the image processor module, and theprocessor may optionally use the EKG signals to time the acquisition ofthe 3-D volumes. In other embodiments, the respiratory signal may alsobe received by the image processor module, and the processor mayoptionally use the respiratory signal to time the acquisition of the 3Dvolumes.

CT volumes may be acquired using a variety of different approaches. Acardiac gated CT volume may be acquired at a particular phase of the EKGcycle. Two variations of cardiac gated CT may include a held-breathversion and a free-breathing version. In the held-breath cardiac gatedCT, the patient is holding their breath (typically either at fullinspiration or full expiration), so that respiration motion is absentwhile the data is acquired. In the free breathing cardiac gated CT, thepatient is breathing freely. The CT volume may be acquired at a desiredpoint of the respiration cycle. By measuring the respiration wave form,the exact respiratory phase at which the CT volume is acquired can beknown (similar to the known cardiac phase at which the CT volume isacquired). In either variation, both the cardiac phase and therespiration cycle phase can be identified for the cardiac gated CT.

A cardiac gated 4-dimensional CT can be generated by acquiring a timeseries of cardiac gated CT volumes at a series of desired EKG phases.Once again, the 4-D cardiac gated CT can be a held-breath type or afree-breathing type (as described above). Additionally, regarding thefree-breathing cardiac gated 4D CT, the resulting series of CT volumesmay be acquired at the same EKG phase, typically throughout therespiration cycle. By associating each CT volume with the associatedphase of the respiration cycle, the time series CT volumes can be usedto model respiratory-induced motion of tissue while minimizing thecardiac motion artifacts.

Yet another type of volume which may be acquired is therespiratory-gated CT volume. Such CT volumes may be acquired at aparticular phase of the respiration cycle. Respiratory gating of CT maybe performed prospectively or retrospectively. The cardiac motion maygenerally be ignored in this type of CT volume, so that the rapidlymoving cardiac structures may be blurry in such CT volumes. In a relatedrespiratory-gated 4-D CT volume, a series of respiratory-gated CTvolumes are acquired at a series of respiratory phases.

Note that the tissue structure which will be targeted need notnecessarily be visible in the image, so long as sufficiently contrastingsurrogate imagable structures are visible in the images to identify thetarget tissue location. The imaging used in many embodiments willinclude a time sequence of three dimensional tissue volumes, with thetime sequence typically spanning one or more cycles (such as a cardiacor heartbeat cycle, a respiration or breathing cycle, and/or the like).

The series of radiation beams are planned, typically by a surgeon usinga user interface (such as a display and keyboard, mouse, or other inputdevice) to communicate with a plan processor module. Based on theimages, a plan 54 will be prepared for treatment of the target tissue,with the plan typically comprising a series of radiation beamtrajectories which intersect within the target tissue. The processormodule may make use of the model (including the tissue movements) todetermine dosages in the target, collateral, and critical or sensitivetissues. The radiation dose within the target tissue should be at leastsufficient to provide the desired effect (often comprising ablation oftissue, inhibition of contractile pathways within the heart, inhibitionof arrhythmogenesis, and/or the like). Radiation dosages outside thetarget tissues will decrease with a relatively steep gradient so as toinhibit damage to collateral tissues, with radiation dosages inspecified sensitive and/or critical tissue structures often being belowa desired maximum threshold to avoid deleterious side effects.Embodiments of the invention may employ the 3-D volumes acquired in theimaging step 52 during the planning 54, with exemplary embodimentsmaking use of the motion model represented by the time sequence of 3-Dtissue volumes so as to more accurately identify exposure of radiationoutside of the target, within sensitive tissue structures, inside thetarget, and the like. Planned timing of some or all of a series ofradiation beams may be established based on the cardiac cycle, therespiration cycle, and/or the like so as to generate the desired dosageswithin the target tissue, so as to minimize or inhibit radiationexposure to critical structures, and/or to provide desired gradientsbetween the target tissue and collateral or sensitive structures. Insome embodiments, the order of the planned radiation beams may bealtered and/or the trajectories of the radiation beams may be calculatedin response to the motion of the model volume.

Once the plan 54 is established, the treatment 56 can be implemented.The treatment will often make use of a processor to direct movement of arobotic structure supporting a radiation beam source, along withregistration, validation, and/or tracking modules which enhance accuracyof the treatment. Tracking may employ the motion model developed duringimaging 52, and/or may also employ a separate intra-operative motionmodel. Alternatively, no motion model will be used, instead the targetlocation computed from real-time image data will be used for tracking.The treatment 56 step and the associated hardware may use a sensorand/or input for physiological wave forms such as the respiration phase,cardiac phase, and the like for use in such tracking.

In one embodiment, an EKG sensor may be coupled to the patient toprovide EKG signals to a targeting processor module. The targetingmodule configures the robot so as to position and orient the linearaccelerator (or other radiation source) toward the target tissue alongthe desired trajectory for a particular radiation beam from among theseries. Once the moving target tissue and the beam trajectory areappropriately aligned, the tracking module may fire the radiation beamby energizing the linear accelerator. Hence, the tracking modulebenefits from the motion model developed during the imaging steps, andthe model may optionally be revised using data obtained immediatelybefore and/or during treatment.

Advantageously, the treatments described herein can be iterative. Ratherthan target many foci or regions as is often done in an invasiveprocedure, externally applied radiosurgical ablation can address one ormore target shapes on one day, and the then other target shapes onanother day as needed. The interim period between treatments can be usedto access the need for subsequent treatments. Such iterative orfractionated treatment is thus more conservative than current methods.

Suitable types of radiation, including particle beam radiation, may beemployed. For example, the present invention encompasses the use of aGammaKnife™ radiosurgery system to ablate the moving tissue. Althoughgamma radiation could be administered during open heart or otherinvasive procedures, the currently preferred applications aresubstantially non-surgical.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modification, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appending claims.

What is claimed is:
 1. A method of radiating a moving target with adesired radiation dose, the target comprising a target tissue havingblood flowing therethrough, the target tissue having a tissue surfaceincluding an inner surface bordering the blood and an outer surface, themethod comprising: acquiring a series of computed tomography (CT)volumes encompassing the target tissue; identifying the target in threedimensions in the acquired CT volumes by visualizing a three dimensionalsurface rendering of the tissue surface of the target tissue andinputting the target with reference to the three dimensional surfacerendering; computing a treatment plan according to the identifiedtarget; computing a dose distribution according to the computedtreatment plan; visualizing a three dimensional display of the dosedistribution superimposed with the three dimensional surface renderingof the tissue surface of the target tissue so as to verify the desiredradiation dose at the target; and delivering the dose distribution tothe target tissue to treat the target.
 2. The method of claim 1, whereinthe step of displaying the visualization of the dose distributioncomprises at least one of: 1) volume rendering, 2) maximum intensityprojection, 3) minimum intensity projection, 4) X-ray projection, 5)haptic feedback, 6) virtual fly-through, 7) stereoscopic 3D rendering,8) virtual reality, and 9) multi-planar, oblique and curvedreconstructions.
 3. The method of claim 1, wherein the treatment plancomprises a plurality of radiation beam trajectories which intersectwithin the target.
 4. The method of claim 1, wherein the targetcomprises a tumor.
 5. The method of claim 1, wherein the targetcomprises heart muscle and wherein the identified target is transmural.6. The method of claim 1, further comprising defining a radiationsensitive structure relative to the acquired CT volumes by visualizingthe three dimensional surface rendering of the tissue surface of thetarget tissue and identifying the radiation sensitive structure withrespect to the three dimensional surface rendering.
 7. The method ofclaim 7, further comprising adjusting the computed treatment plan basedon the defined radiation sensitive structure.
 8. The method of claim 1,further comprising registering a three dimensional electrogram with theacquired CT volumes.
 9. The method of claim 1, further comprisingacquiring a pair of images of the target during treatment andregistering the CT volumes with the pair of images to check a positionof the target during treatment.
 10. The method of claim 1, wherein theidentified target is non-isocentric.
 11. The method of claim 1, furthercomprising expanding the identified target with a margin that is basedon motion estimates.
 12. The method of claim 11, wherein the marginincludes the identified target during at least 80% of a target motiontime.
 13. A non-transitory computer-readable storage medium comprising aset of computer executable instructions for treating a moving target,the target comprising a target tissue having blood flowing therethrough,the target tissue having a tissue surface including an inner surfacebordering the blood and an outer surface, wherein execution of theinstructions by a computer processor causes the processor to carry outthe steps of: receiving a series of computed tomography (CT) volumesencompassing the target tissue; displaying on a display device a threedimensional surface rendering of the target tissue; receiving user inputdefining the target in three dimensions with reference to the threedimensional surface rendering of the target tissue; computing atreatment plan according to the user identified target; computing a dosedistribution according to the computed treatment plan; displaying on thedisplay device a three dimensional visualization of the dosedistribution superimposed with the three dimensional surface renderingof the tissue surface of the target tissue; and delivering the dosedistribution to the target tissue to treat the target.
 14. Thenon-transitory computer-readable storage medium of claim 13, wherein theprocessor carries out the step of displaying the dose distribution byutilizing at least one of: 1) volume rendering, 2) maximum intensityprojection, 3) minimum intensity projection, 4) X-ray projection, 5)haptic feedback, 6) virtual fly-through, 7) stereoscopic 3D rendering,8) virtual reality, and 9) multi-planar, oblique and curvedreconstructions.
 15. The non-transitory computer-readable storage mediumof claim 13, wherein the treatment plan comprises a plurality ofradiation beam trajectories which intersect within the target.
 16. Thenon-transitory computer-readable storage medium of claim 13, wherein theprocessor further carries out a step of receiving user input defining aradiation sensitive structure with respect to the three dimensionalsurface rendering of the target tissue.
 17. The non-transitorycomputer-readable storage medium of claim 16, wherein the processorfurther carries out a step of adjusting the computed treatment planbased on the user defined radiation sensitive structure.
 18. Thenon-transitory computer-readable storage medium of claim 13, wherein theprocessor further carries out a step of registering a three dimensionalelectrogram with the received CT volumes.
 19. The non-transitorycomputer-readable storage medium of claim 13, wherein the processorfurther carries out a step of receiving a pair of images of the targetduring treatment and a step of registering the CT volumes with the pairof images to check a position of the target during treatment.
 20. Thenon-transitory computer-readable storage medium of claim 13, wherein theprocessor further carries out a step of expanding the identified targetwith a margin that is based on motion estimates.
 21. A system forradiating a moving target inside a tissue or on a blood vessel, thesystem comprising: an image receiving apparatus for receiving CT volumesencompassing the target; a user input device for receiving user inputdefining a radiation target region with reference to a three dimensionalsurface rendering of the target tissue; a processor coupled with theimage receiving apparatus and the user input device, the processorconfigured to: i) compute a treatment plan according to the receiveduser input defining the radiation target region, ii) compute a dosedistribution according to the computed treatment plan; iii) generate thethree dimensional surface rendering of the target tissue using thereceived CT volumes; (iv) generate a three dimensional surface renderingof the dose distribution; a display coupled with the processor fordisplaying the three dimensional surface rendering of the target tissueand the three dimensional surface rendering of the dose distribution;and a radiation delivery device coupled with the processor, theradiation delivery device configured to deliver radiation to the targetregion according to the computed dose distribution.
 22. The system ofclaim 21, wherein the user input device is further configured to receiveuser input defining a radiation sensitive structure relative to thethree dimensional surface rendering of the target tissue.
 23. The systemof claim 22, wherein the processor is further configured to adjust thecomputed treatment plan based on the user defined radiation sensitivestructure.
 24. The system of claim 21, wherein the processor is furtherconfigured to register a three dimensional electrogram with the receivedCT volumes.
 25. The system of claim 21, further comprising an imageguidance system, the image guidance system configured to acquire a pairof images of the target during treatment and to register the CT volumeswith the pair of images to check a position of the target duringtreatment.
 26. The method of claim 1, wherein the series of CT volumescomprises a time series of CT volumes distributed throughout a movementcycle of the moving target; wherein a dose distribution is calculatedfor each of the received CT volumes; and wherein the step of visualizinga three dimensional display of the dose distribution comprisesvisualizing a four dimensional display of the dose distribution.
 27. Thenon-transitory computer-readable storage medium of claim 13, wherein theseries of CT volumes comprises a time series of CT volumes distributedthroughout a movement cycle of the moving target; wherein a dosedistribution is calculated for each of the received CT volumes; andwherein the step of displaying comprises displaying on the displaydevice a four dimensional display of the dose distribution.
 28. Thesystem of claim 21, wherein the image receiving apparatus is configuredto receive a time series of CT volumes distributed throughout a movementcycle of the moving target; wherein processor is further configured tocalculate a dose distribution for each of the received CT volumes; andwherein the display is configured to display a four dimensional surfacerendering of the dose distribution.